(S)-1-[3,5-Bis­(trifluoro­meth­yl)phen­yl]-N-methylethyl­amine–(R)-2-hydroxy­butane­dioic acid (1/1)

Hai-Bin Zhu; Jun-Feng Ji; Hai Wang

doi:10.1107/S1600536808043201

. 2008 Dec 24;65(Pt 1):o197. doi: 10.1107/S1600536808043201

(S)-1-[3,5-Bis(trifluoromethyl)phenyl]-N-methylethylamine–(R)-2-hydroxybutanedioic acid (1/1)

Hai-Bin Zhu ^a,^*, Jun-Feng Ji ^a, Hai Wang ^a

PMCID: PMC2968104 PMID: 21581651

Abstract

In the title compound, C₁₁H₁₁F₆N·C₄H₆O₅, a key intermediate in the synthesis of the NK1 receptor antagonist of casopitant, the F atoms of the trifluoromethyl groups are disordered over two sites with equal occupancies. In the crystal, the components are linked by bifurcated N—H⋯(O,O) hydrogen bonds.

Related literature

The title compound is a key intermediate for the synthesis of casopitant, which is an NK1 receptor antagonist (Humphrey, 2003 ▶) for the treatment of chemotheraphy-induced nausea and vomiting (CINV) (Lohr, 2008 ▶).

Experimental

Crystal data

C₁₁H₁₁F₆N·C₄H₆O₅
M _r = 405.30
Monoclinic,
a = 6.6770 (13) Å
b = 8.4510 (17) Å
c = 16.366 (3) Å
β = 100.05 (3)°
V = 909.3 (3) Å³
Z = 2
Mo Kα radiation
μ = 0.15 mm⁻¹
T = 298 (2) K
0.30 × 0.10 × 0.10 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: ψ scan (North et al., 1968 ▶) T _min = 0.957, T _max = 0.985
1915 measured reflections
1757 independent reflections
1067 reflections with I > 2σ(I)
R _int = 0.058
3 standard reflections every 200 reflections intensity decay: 1%

Refinement

R[F ² > 2σ(F ²)] = 0.063
wR(F ²) = 0.154
S = 1.00
1757 reflections
220 parameters
2 restraints
H-atom parameters constrained
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.27 e Å⁻³

Data collection: CAD-4 Software (Enraf–Nonius,1989 ▶); cell refinement: CAD-4 Software; data reduction: XCAD4 (Harms & Wocadlo, 1995 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808043201/at2692sup1.cif

e-65-0o197-sup1.cif^{(21.1KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808043201/at2692Isup2.hkl

e-65-0o197-Isup2.hkl^{(86.5KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N—H0A⋯O4ⁱ	0.86	2.37	2.914 (7)	122
N—H0A⋯O3ⁱⁱ	0.86	2.20	2.887 (7)	137

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

The authors thank the China Postdoctoral Research Fund (20070411010) and the Young Teachers’ Starting Fund of Southeast University for support.

supplementary crystallographic information

Comment

The title compound, C₁₁H₁₁F₆N.C₄H₆O₅, is a key intermediate for the synthesis of casopitant, which is an NK1 receptor antagonist (Humphrey, 2003) for the treatment of chemotheraphy-induced nausea and vomiting (CINV) (Lohr, 2008).

The molecular structure of the title compound is shown in Fig.1. The F atoms of the trifluoromethyl group are disordered over two sites in a 0.50:0.50 ratio. N—H···O hydrogen bonding interactions occur between (S)-1-(3, 5-bis(trifluoromethyl)-phenyl)ethylamine N-monomethyl and (R)-2-hydroxybutanedioic acid (Table 1).

Experimental

To a solution of 3, 5-bis(trifluoromethyl)-phenyl)ethylamine N-monomethyl (2.71 g, 10 mmol) in EtOAc (25 ml), (R)-2-hydroxybutanedioic acid (1.34,10 mmol) was added portionwise. The suspension was stirred for 2h at 298 K, then for 3 h at 273 K. The suspension was filtered and the cake was washed with EtOAc (20 ml). The solid was dried under vacucum obtaining the crude title compound (1.48 g). Single crystal of the title compound suitable for X-ray diffraction was obtained by slow evaporation of the EtOAc solution of the title compound.